{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:11:28Z","timestamp":1790777488469,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T00:00:00Z","timestamp":1634342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation Fighting Blindness","award":["Grant PPA-0717- 0719-RAD"],"award-info":[{"award-number":["Grant PPA-0717- 0719-RAD"]}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["Grant agreement No. 722717 \u2013 project OCUTHER"],"award-info":[{"award-number":["Grant agreement No. 722717 \u2013 project OCUTHER"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Maloch Stiftung","award":["Personal grant to Marius Ueffing"],"award-info":[{"award-number":["Personal grant to Marius Ueffing"]}]},{"name":"ProRetina Foundation","award":["to Marius Ueffing"],"award-info":[{"award-number":["to Marius Ueffing"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Rhodopsin (RHO) misfolding mutations are a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). The most prevalent mutation, RHOP23H, results in its misfolding and retention in the endoplasmic reticulum (ER). Under homeostatic conditions, misfolded proteins are selectively identified, retained at the ER, and cleared via ER-associated degradation (ERAD). Overload of these degradation processes for a prolonged period leads to imbalanced proteostasis and may eventually result in cell death. ERAD of misfolded proteins, such as RHOP23H, includes the subsequent steps of protein recognition, targeting for ERAD, retrotranslocation, and proteasomal degradation. In the present study, we investigated and compared pharmacological modulation of ERAD at these four different major steps. We show that inhibition of the VCP\/proteasome activity favors cell survival and suppresses P23H-mediated retinal degeneration in RHOP23H rat retinal explants. We suggest targeting this activity as a therapeutic approach for patients with currently untreatable adRP.<\/jats:p>","DOI":"10.3390\/biom11101528","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:13:32Z","timestamp":1634512412000},"page":"1528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacological Inhibition of the VCP\/Proteasome Axis Rescues Photoreceptor Degeneration in RHOP23H Rat Retinal Explants"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-4493","authenticated-orcid":false,"given":"Merve","family":"Sen","sequence":"first","affiliation":[{"name":"Centre of Ophthalmology, Institute for Ophthalmic Research, Elfriede-Aulhorn-Strasse 7, 72076 T\u00fcbingen, Germany"},{"name":"Graduate Training Centre of Neuroscience, University of T\u00fcbingen, \u00d6sterbergstrasse 3, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-6916","authenticated-orcid":false,"given":"Oksana","family":"Kutsyr","sequence":"additional","affiliation":[{"name":"Department of Physiology, Genetics and Microbiology, University of Alicante, E-03080 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Cao","sequence":"additional","affiliation":[{"name":"Centre of Ophthalmology, Institute for Ophthalmic Research, Elfriede-Aulhorn-Strasse 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Bolz","sequence":"additional","affiliation":[{"name":"Centre of Ophthalmology, Institute for Ophthalmic Research, Elfriede-Aulhorn-Strasse 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9045-182X","authenticated-orcid":false,"given":"Blanca","family":"Arango-Gonzalez","sequence":"additional","affiliation":[{"name":"Centre of Ophthalmology, Institute for Ophthalmic Research, Elfriede-Aulhorn-Strasse 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2209-2113","authenticated-orcid":false,"given":"Marius","family":"Ueffing","sequence":"additional","affiliation":[{"name":"Centre of Ophthalmology, Institute for Ophthalmic Research, Elfriede-Aulhorn-Strasse 7, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.cell.2015.03.032","article-title":"Widespread proteome remodeling and aggregation in aging C. elegans","volume":"161","author":"Walther","year":"2015","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lualdi, M., Alberio, T., and Fasano, M. 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